A Reference Range for Endogenous Gamma-Hydroxybutyrate in Urine by Gas Chromatography-Mass Spectrometry

Abstract

Gamma-hydroxybutyrate (GHB) has been implicated in drug-facilitated sexual assault (DFSA). The interpretation of GHB levels in biological samples collected for evidence is complicated by the natural presence of this compound in the body, and by its extremely rapid elimination after ingestion. There is a lack of agreement regarding a suitable cut-off concentration, which can reliably separate endogenous concentrations in urine from those reflecting ingestion. We have developed a method for the analysis of low levels of GHB in urine and have used it to establish a reference range for normal females. The method uses liquid-liquid extraction, silyl-derivatization, and gas chromatographic-mass spectrometric analysis. The limit of detection was 0.1 mg/L, and the method was linear from 0.1 to 5.0 mg/L. Our analysis of 50 urine samples donated by normal women indicates an upper limit of normal for urinary GHB of 1.46 mg/L or 323 microg GHB/mmol of creatinine. We propose that a 5 mg/L cut-off for urine GHB concentration, or 1000 microg GHB/mmol creatinine, will separate endogenous GHB concentrations from those reflecting GHB ingestion in antemortem samples with greater than 99% confidence, providing that a specific assay method comparable with that we describe is used. We demonstrate that urinary GHB concentrations fall with age and that this can be corrected for by measurement of the GHB/creatinine ratio.

Gamma-hydroxybutyric acid stability and formation in blood and urine

“…Due to the growing number of cases of overdose or sexual assault where GHB application is suspected, there are increasing demands for routine toxicological examinations in laboratories. However, the interpretation of data related to biological specimens and pos-tmortem blood in particular, has become very problematic and controversial, as has been shown previously by many authors [7][8][9][10][11][12][13][14][15][16][17].…”

Evidence for Elevated Endogenous Urinary Gamma-Hydroxybutyric Acid Levels: Two Case Reports

“…However, there is still a slight lack of agreement regarding the GHB cut-off value. Crookes et al [13] developed a unique method for analysis of low levels of GHB in urine. This method consisted of liquidliquid extraction, silyl-derivatization, and GC-MS analysis to analyze the urine samples of 50 sexually active women between the ages of 14 and 52 years.…”

Une série de nouveaux cas d’intoxications par le GHB ou la GBL. Dosages dans le sang, l’urine et les phanères

“…Chez le vivant, les concentrations physiologiques sont inférieures à 2 mg/L dans le sang et 10 mg/L dans l'urine selon le consensus de la Société de Toxicologie de Belgique et du Luxembourg (BLT, 9 novembre 2000) et un groupe d'expert de l'UNODC [4]. Les dernières valeurs endogènes du GHB dans l'urine publiées sont les suivantes : -0,00-2,70 mg/L (n = 207) [5] -0,16-2,14 mg/L, volontaires sains [6] -0,17-3,03 mg/L, diabétiques [6] -<1,46 mg/L (n = 50) [7] -0,64-4,20 (n = 50) [8].…”